The objective of the proposed research is to further explore the relationship between structure and biological activity in the actinomycin series, and to synthesize analogues which might prove to be more effective antitumor agents than actinomycin D. These analogues will vary at three different amino acid sites in the molecule. One new approach to improvement in selectivity involves conjugation of one of these actinomycins with the tumor-specific lectin, concanavalin A. Further structural and biosynthetic studies on naturally occurring actinomycins of the Z complex, and physicochemical investigations of the binding of various actinomycins to DNA, will also be undertaken. The methods to be employed include total synthesis of actinomycin analogues and their purification by chromatographic procedures, nuclear magnetic resonance studies on these actinomycins and synthetic cyclopeptide intermediates, and spectral studies of the binding of these actinomycins to DNA. The actinomycin analogues produced in this project will be submitted to NCI for evaluation of their antitumor efficacy.